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Elnagi EA, AL-Maqati TN, Alnaam Y, Adam AA, Rabaan AA, Mohamed ZS, Amer A, Almarfoi HL. The prevalence of SEN virus among blood donors in the Eastern Province of KSA. Saudi J Biol Sci 2021; 28:3922-3925. [PMID: 34220248 PMCID: PMC8241597 DOI: 10.1016/j.sjbs.2021.03.067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 03/24/2021] [Accepted: 03/25/2021] [Indexed: 11/29/2022] Open
Affiliation(s)
- Elmoeiz A. Elnagi
- Clinical Laboratory Sciences Department, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | - Thekra N. AL-Maqati
- Clinical Laboratory Sciences Department, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | - Yaser Alnaam
- Clinical Laboratory Sciences Department, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | - Ahmed A. Adam
- Clinical Laboratory Sciences Department, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | - Ali A. Rabaan
- Molecular Diagnostic Laboratory, Johns Hopklins Aramco Healthcare, Dhahran, Saudi Arabia
| | - Zeinab S. Mohamed
- Faculty of Clinical Laboratory Sciences, Alzaiem Alazhari University, Khartoum, Sudan
| | - Anisah Amer
- Clinical Laboratory Sciences Department, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
| | - Hussa L. Almarfoi
- Clinical Laboratory Sciences Department, Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia
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Gautam S, Sigdel KR, Adhikari S, Basnyat B, Paudyal B, Poudel J, Risal U. Case Report: Pulmonary tuberculosis and raised transaminases without pre-existing liver disease- Do we need to modify the antitubercular therapy? Wellcome Open Res 2020; 5:193. [PMID: 33102787 PMCID: PMC7569747 DOI: 10.12688/wellcomeopenres.16175.2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/12/2020] [Indexed: 11/20/2022] Open
Abstract
We report a case of an adult female with pulmonary tuberculosis who had biochemical evidence of liver injury during the presentation manifested as raised transaminases, but without clinically obvious pre-existing liver disease nor a history of hepatotoxic drug use. This is a fairly common scenario seen in tuberculosis endemic areas; however, this is an under reported condition in the literature and guidelines for its management has not been established. Many clinicians including the authors have treated such cases with modified liver friendly regimens in fear of increasing the hepatotoxicity with standard antitubercular drugs. However, the modified regimens may not be optimal in treating the underlying tuberculosis. In this report, we gave full dose standard drugs, and the liver injury resolved as evidenced by normalization of transaminases. Further research is required in this regard, but the presence of transaminitis with no obvious common underlying etiology may not warrant a modification of standard antitubercular regimen.
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Affiliation(s)
- Sanjeev Gautam
- Internal Medicine, Patan Academy of Health Sciences, Lalitpur, State 3, Nepal
| | - Keshav Raj Sigdel
- Internal Medicine, Patan Academy of Health Sciences, Lalitpur, State 3, Nepal
| | - Sudeep Adhikari
- Internal Medicine, Patan Academy of Health Sciences, Lalitpur, State 3, Nepal
| | - Buddha Basnyat
- Internal Medicine, Patan Academy of Health Sciences, Lalitpur, State 3, Nepal.,Oxford University Clinical Research Unit, Patan Hospital, Lalitpur, State 3, Nepal
| | - Buddhi Paudyal
- Internal Medicine, Patan Academy of Health Sciences, Lalitpur, State 3, Nepal
| | - Jiwan Poudel
- Internal Medicine, Patan Academy of Health Sciences, Lalitpur, State 3, Nepal
| | - Ujjwol Risal
- Internal Medicine, Patan Academy of Health Sciences, Lalitpur, State 3, Nepal
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Li G, Zhou Z, Yao L, Xu Y, Wang L, Fan X. Full annotation of serum virome in Chinese blood donors with elevated alanine aminotransferase levels. Transfusion 2019; 59:3177-3185. [PMID: 31393615 DOI: 10.1111/trf.15476] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 07/14/2019] [Accepted: 07/20/2019] [Indexed: 12/30/2022]
Abstract
BACKGROUND A serum alanine aminotransferase (ALT) test is currently demanded for blood donation in China. One of the major reasons to include such a test is possible etiology of known or unknown hepatotropic viruses. However, this hypothesis has never been examined convincingly. STUDY DESIGN AND METHODS The study recruited 90 Chinese blood donors that were divided into three groups based on their ALT values. Serum virome from these donors was explored using a metagenomics approach with enhanced sensitivity resolved at single sequencing reads. RESULTS Anellovirus and pegivirus C (GBV-C) were detected among these donors. None of them were found solely in donors with abnormal liver enzyme. Anellovirus was highly prevalent (93.3%) and the co-infection with multiple genera (alpha, beta, and gammatorquevirus) were more common in the donors with normal ALT values in comparison to those with elevated ALT (single/double/triple Anellovirus genera, 1/3/24 vs. 7/7/14 or 6/7/13, p = 0.009). For unmapped reads that accounted for 15 ± 14.9% of the data, similarity-based (BLASTN, BLASTP, and HMMER3) and similarity-independent (k-mer frequency) analysis identified several circular rep encoding ssDNA (CRESS-DNA) genomes. Direct PCR testing indicated these genomes were likely reagent contaminants. CONCLUSION Viral etiology is not responsible for elevated ALT levels in Chinese blood donors. The ALT test, if not abandoned, should be adjusted for its cutoff in response to donor shortage in China.
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Affiliation(s)
- Gang Li
- Wuhan Blood Center, Wuhan, China
| | | | - Li Yao
- Wuhan Blood Center, Wuhan, China
| | - Yanjuan Xu
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri
| | - Lan Wang
- Wuhan Blood Center, Wuhan, China
| | - Xiaofeng Fan
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri.,Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, Missouri
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Gaze R, Carvalho DMD, Santoro-Lopes G, Tura LFR. Das hepatopatias e icterícias às hepatites virais: configuração de um caleidoscópio. Rev Saude Publica 2013; 47:116-22. [DOI: 10.1590/s0034-89102013000100015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2011] [Accepted: 06/28/2012] [Indexed: 11/22/2022] Open
Abstract
As hepatites virais A, B, C, D e E - viroses sistêmicas hepatotrópicas - produzem quadros de hepatite aguda. Dependendo do agente etiológico, da carga viral e de condições do hospedeiro, podem evoluir para hepatite crônica, cirrose, câncer de fígado e formas agudas fulminantes. A versatilidade ecológica desses vírus configura uma natureza espectral e cambiante de transmissão no tempo e no espaço; potencializada pelo curso subclínico por vezes prolongado de grande parte das infecções, constitui-se em desafio epidemiológico. Com base no curso histórico dessas infecções foram descritos cenários e tendências relativas ao seu comportamento socioepidemiológico, apontando para a necessidade de superar modelos, padrões, protocolos e retornar à investigação de cada situação de saúde/doença. Ou seja, assinala para a imprescindível exploração das singularidades no sentido de desenvolver ações gerais modeladas pelas especificidades locais.
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Abdelwahab SF, Zakaria Z, Sobhy M, Rewisha E, Mahmoud MA, Amer MA, Del Sorbo M, Capone S, Nicosia A, Folgori A, Hashem M, El-Kamary SS. Hepatitis C virus-multispecific T-cell responses without viremia or seroconversion among Egyptian health care workers at high risk of infection. CLINICAL AND VACCINE IMMUNOLOGY : CVI 2012; 19:780-6. [PMID: 22441392 PMCID: PMC3346335 DOI: 10.1128/cvi.00050-12] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatitis C virus (HCV)-specific cell-mediated immunity (CMI) has been reported among exposed individuals without viremia or seroconversion. Limited data are available regarding CMI among at-risk, seronegative, aviremic Egyptian health care workers (HCW), where HCV genotype 4 predominates. We investigated CMI responses among HCW at the National Liver Institute, where over 85% of the patients are HCV infected. We quantified HCV-specific CMI in 52 seronegative aviremic Egyptian HCW using a gamma interferon (IFN-γ) enzyme-linked immunospot assay in response to 7 HCV genotype 4a overlapping 15-mer peptide pools covering most of the viral genome. A positive HCV-specific IFN-γ response was detected in 29 of 52 HCW (55.8%), where 21 (40.4%) had a positive response for two to seven HCV pools and 8 (15.4%) responded to only one pool. The average numbers of IFN-γ total spot-forming cells (SFC) per million peripheral blood mononuclear cells (PBMC) (± standard error of the mean [SEM]) in the 29 responding and 23 nonresponding HCW were 842 ± 141 and 64 ± 15, respectively (P < 0.001). Flow cytometry indicated that both CD4(+) and CD4(-) T cells produced IFN-γ. In summary, more than half of Egyptian HCW demonstrated strong HCV multispecific CMI without viremia or seroconversion, suggesting possible clearance of low HCV exposure(s). These data suggest that detecting anti-HCV and viremia to determine past exposure to HCV can lead to an underestimation of the true disease exposure and that CMI response may contribute to the low degree of chronic HCV infection in these HCW. These findings could have strong implications for planning vaccine studies among populations with a high HCV exposure rate. Further studies are needed to determine whether these responses are protective.
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Affiliation(s)
- Sayed F Abdelwahab
- Department of Microbiology and Immunology, Faculty of Medicine, Minia University, Minia, Egypt.
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Epidemiological characteristics and clinical manifestations of acute non-A-E hepatitis. VOJNOSANIT PREGL 2010; 67:903-9. [DOI: 10.2298/vsp1011903d] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Background/Aim. Acute non-A, non-B, non-C, non-D, non-E hepatitis (non-A-E AH) is an acute disease of the liver of unknown etiology for which one or more new, so far undetected, hepatotropic viruses may be responsible. The frequency of non-A-E AH ranges from 3.8% to 33.9%, and therefore it has a significant place within current infectology and hepatology. The aim of our study was to establish the frequency, clinical and biochemical characteristics, natural course and outcome of non-A-E AH and compare them with control groups affected by acute viral hepatitis A, B and C. Methods. This descriptive-analytic prospective study included 31 patients with non-A-E AH treated at the Institute of Infectious and Tropical Diseases, Clinical Center of Serbia, Belgrade, from 2003 to 2008. They were followed up during the period not less than 6 months. The controls involved randomly selected patients, treated at the same time with a definite diagnosis of acute viral hepatitis A, B and C. Statistical data analysis used Mann-Whitney Utest, Student's t-test and variance analysis. The value of p < 0.05 was considered statistically significant. Results. The frequency of non-A-E AH was 7.6%. Almost no difference was found between sexes (male/female ratio was 1 : 1.07); it was developed in all age groups, with the highest incidence in the middle age (mean age was 38.32 ? 15.3 years). It appeared equally throughout the whole year. Out of risk factors, inoculation risk was predominant (before all, dental interventions), mostly involving urban population living in comfortable conditions. The duration of incubation varied much ranging from 20 to 180 days (median 60 days). By clinical course, moderate and icteric forms were most common, mostly corresponding to acute hepatitis A and C. On the other hand, by duration of the disease (mean duration was 67.1 ? 27.1) and chronic transformation, non-A-E AH resembled to acute hepatitis B. Progression to chronicity was recorded in 9.68% of the patients. There was no fulminant neither cholestatic form of the disease. Conclusion. Based on the results obtained in this study, it is probable that there are some so far undetected primary hepatotropic viruses in our environment.
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Tassopoulos NC, Papatheodoridis GV, Delladetsima I, Hatzakis A. Clinicopathological features and natural history of acute sporadic non-(A-E) hepatitis. J Gastroenterol Hepatol 2008; 23:1208-15. [PMID: 18554239 DOI: 10.1111/j.1440-1746.2008.05454.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
AIM The aim of the present study was to describe the clinicopathological characteristics and the natural history of acute non-(A-E) hepatitis and to assess the possible role of hepatitis G virus (HGV), TT virus (TTV) and mainly SEN virus (SENV). METHODS A cohort of 55 patients with sporadic acute non-(A-E) hepatitis with a mean follow up of 31 (6-55) months was studied. RESULTS The clinical presentation was fulminant in one (1.8%), protracted with impaired regeneration in seven (12.7%) and benign in the remaining 47 (85.5%) cases. Progression to chronic hepatitis was observed in 15 (27.3%) patients; it was more frequent in clinically severe than in non-severe cases (five of eight patients or 62.5% vs 10 of 47 patients or 21.3%, P = 0.028). Six of 10 biopsied chronic non-(A-E) cases developed cirrhosis within 10-33 months. Serum HGV-RNA was detected in 16 of 55 (29.1%) patients, TTV in 20 of 38 (52.6%) patients and SENV-D/H DNA in 20 of 55 (36.4%) cases. HGV-RNA was detected more frequently in clinically severe than in non-severe cases (five of eight or 62.5% vs 11 of 47 or 23.4%, P = 0.038). There was no other association between the presence of HGV, TTV, or SENV infection and patient characteristics or severity and outcome of disease. CONCLUSIONS HGV, TTV, and SENV do not seem to be responsible for the majority of sporadic acute non-(A-E) hepatitis cases. Our cohort further supports the existence of new, unknown hepatitis agent(s) with uncertain mode of transmission. The non-(A-E) agent(s) can also cause chronic hepatitis, which often has an aggressive course with rapid development of cirrhosis.
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Affiliation(s)
- Nicolaos C Tassopoulos
- National Retrovirus Reference Center, Department of Hygiene and Epidemiology, Athens University Medical School, Athens, Greece.
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Schréter I, Kristian P, Jarcuska P, Porubcin S, Siegfried L, Birosová E, Rajnic A, Gocalová A. Detection of SEN virus in the general population and different risk groups in Slovakia. Folia Microbiol (Praha) 2006; 51:223-8. [PMID: 17004654 DOI: 10.1007/bf02932126] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Sera of 426 adult persons were examined to assess the prevalence of SEN virus (SENV) infection in Slovakia and to determine the importance of different risk factors for parenteral transmission. SENV prevalence was determined by the PCR method using primers of SENV-D and SENV-H strains. Positive results were found in 10 of 37 patients with acute hepatitis of unknown etiology, 7 of 38 with acute hepatitis B, 17 of 44 with chronic hepatitis B, 29 of 102 with chronic hepatitis C, 36 of 72 hemodialysis patients, 2 of 33 health care workers and 24 of 100 persons from the control group. The highest prevalence of SENV was among hemodialysis patients, significantly higher than in the groups of health care workers, acute hepatitis B and controls. The lowest prevalence was in health care workers group, significantly lower also in comparison with groups of chronic hepatitis B and C. Among the possible risk factors of virus transmission the average duration of hemodialysis (1.15 vs. 0.50 years), number of surgeries (1.60 vs. 1.10) and transfusions (1.34 vs. 0.94) showed notable differences in terms of SENV infection. Bilirubin and aminotransferase levels did not differ between SENV-positive and -negative groups. No pathogenetic role of SEN virus in liver injury was confirmed.
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Affiliation(s)
- I Schréter
- Department of lnfectious Diseases, Faculty of Medicine, P.J. Safárik University, 041 90 Kosice, Slovakia.
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Paraná R, Codes L, Andrade Z, Freitas LARD, Santos-Jesus R, Reis M, Cotrim H, Cunha S, Trepo C. Clinical, histologic and serologic evaluation of patients with acute non-A-E hepatitis in north-eastern Brazil: is it an infectious disease? Int J Infect Dis 2004; 7:222-30. [PMID: 14563227 DOI: 10.1016/s1201-9712(03)90056-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Non-A-E hepatitis and acute cryptogenic hepatitis are the names given to the disease of patients with clinical hepatitis, but in whom serologic evidence of A-E hepatitis has not been found. Over a period of 8 years, we evaluated in Brazil 32 patients who fulfilled the criteria for this diagnosis in order to determine patterns of the clinical illness, laboratory parameters, or histologic features. Each patient was subjected to virologic tests to exclude A-E hepatitis and cytomegalovirus/Epstein-Barr virus infection. Drug-induced hepatitis and autoimmune disease were also excluded. Wilson's disease was excluded in young patients. The course of the disease was clinical/biochemical recovery in 3 months in 25 patients and persistent alanine aminotransferase (ALT) elevation in 7 patients. Three of these had chronic hepatitis, and one had severe fibrosis on liver biopsy. During the acute illness, mean peak ALT was 1267 IU/L, bilirubin was 4.0 mg/dL, and ferritin was 1393 IU/mL. GB virus type C (GBV-C) was found in six patients, and TT virus (TTV) in five patients. We conclude that, in Brazil, non-A-E hepatitis probably originates from still unidentified viruses. The course of the disease and the histologic patterns are similar to those recorded for known viruses. Continuous survey for the specific etiologic agents is needed.
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Affiliation(s)
- Raymundo Paraná
- Gastro-Hepatology Unit, University Hospital of Bahia, Bahia, Brazil,CPgMS-UFBA, Bahia-Salvador, Brazil.
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Tang W, Peng XM, Zhang Y, Wang H, Jiang XL, Zhou BP. Establishment and application of polymerase chain reaction for detecting D and H subtypes of SEN virus. Shijie Huaren Xiaohua Zazhi 2003; 11:1540-1543. [DOI: 10.11569/wcjd.v11.i10.1540] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To establish a polymerase chain reaction (PCR) method to detect 2 SENV subtypes (SENV-D and SENV-H) in sera from patients with hepatitis and healthy adults.
METHODS The outer primers were designed based on the data of SENV D and H subtypes from geneBank, while sequences of the inner pair of primers were obtained from newly published medical literature, both of which were used to establish a nested-PCR. SENV-D and H in sera from 192 healthy adults and 48 patients with acute hepatitis A, 176 with chronic hepatitis B, 98 with chronic hepatitis C, and 38 with non A-E hepatitis were detected by this method.
RESULTS The specificity and sensitivity of the nested-PCR test were perfect. The prevalence of SENV-D and/or SENV-H (SENV-D/H) infections in healthy adults and patients with acute hepatitis A, chronic hepatitis B, chronic hepatitis C and non A-E hepatitis were 30.7%, 37.5%, 64.8%, 57.1% and 44.7%, respectively. SENV D/H infection were more frequent in patients with chronic hepatitis B and chronic hepatitis C than in healthy adults (P<0.001), but showed no significant difference between patients with non A-E and healthy adults (P>0.05).
CONCLUSION This nested PCR can be used to detect SEN virus. SENV infections do occur in Shenzhen. SENV may share similar modes of transmission to that of HBV and HCV, but whether it plays a causal role in non A-E hepatitis remains to be elucidated.
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Affiliation(s)
- Wei Tang
- Shenzhen Research Institute of Liver Disease, Shenzhen East Lake Hospital, Shenzhen 518020, Guangdong Province, China
| | - Xiao-Mou Peng
- Department of Infectious Disease, The Third Affiliated Hospital of Zhongshan University, Guangzhou 510630, Guangdong Province, China
| | - Ying Zhang
- Shenzhen Research Institute of Liver Disease, Shenzhen East Lake Hospital, Shenzhen 518020, Guangdong Province, China
| | - Hui Wang
- Shenzhen Research Institute of Liver Disease, Shenzhen East Lake Hospital, Shenzhen 518020, Guangdong Province, China
| | - Xiao-Ling Jiang
- Shenzhen Research Institute of Liver Disease, Shenzhen East Lake Hospital, Shenzhen 518020, Guangdong Province, China
| | - Bo-Ping Zhou
- Shenzhen Research Institute of Liver Disease, Shenzhen East Lake Hospital, Shenzhen 518020, Guangdong Province, China
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Lin JG, Goto T, Nakane K, Miura K, Mikami KI, Ohshima S, Yoneyama K, Watanabe S. Clinical significance of SEN-virus on interferon response in chronic hepatitis C patients. J Gastroenterol Hepatol 2003; 18:1144-9. [PMID: 12974900 DOI: 10.1046/j.1440-1746.2003.02946.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
BACKGROUND AND AIM A novel virus, SEN-virus (SENV), was recently discovered. It has been reported as a candidate for a non-A-E hepatitis virus. However, much is still unknown about the clinical significance of SENV. The aim of the present study was to clarify the clinical significance of SENV in patients coinfected with SENV and hepatitis C virus (HCV). METHODS The 52 subjects had chronic hepatitis C and had undergone interferon (IFN) therapy. SEN virus DNA was investigated by using polymerase chain reaction with SENV-specific primers, which we designed to detect all strains of SENV. Additionally, SENV-D and -H were detected by consensus primers. RESULTS Thirty-five patients were SENV-DNA positive and 22 patients were SENV-D- or -H-positive before IFN therapy. After IFN therapy, in the HCV-RNA eradication group, all cases normalized their serum alanine aminotransferase (ALT). However, in the no eradication group, the ALT no-response rate was 68.7%. In contrast, in the SENV eradication group, the ALT no-response rate was 51.9%, and in the no eradication group, it was 37.5%. Also, in the SENV-D and -H eradication group, the ALT no-response rate was 54.5%, and in the no eradication group, it was 36.4%. The changes in ALT after IFN therapy were significantly correlated with the changes in HCV RNA, but no correlation was found with the SENV DNA presence. CONCLUSIONS Hepatocellular injury in patients with chronic hepatitis who are coinfected with HCV and SENV appears to primarily be caused by HCV, and is less attributable to SENV.
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Affiliation(s)
- Jiun-Guey Lin
- First Department of Internal Medicine, Akita University School of Medicine, Akita, Japan
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12
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Kleinman S, Chan P, Robillard P. Risks associated with transfusion of cellular blood components in Canada. Transfus Med Rev 2003; 17:120-62. [PMID: 12733105 DOI: 10.1053/tmrv.2003.50009] [Citation(s) in RCA: 195] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
We provide a comprehensive review of risks associated with allogeneic red blood cell and platelet transfusions in Canada. The review focuses on clinically symptomatic noninfectious transfusion risks (acute and delayed hemolytic, febrile nonhemolytic [FNHTR], allergic, volume overload, transfusion-related acute lung injury, graft-versus-host disease, and posttransfusion purpura) and the risk of clinically significant disease from transfusion-transmitted infections. Data sources include information from Canadian Blood Services, Héma-Québec, Health Canada, and the Québec Hemovigilance System as well as published information from research studies and international hemovigilance systems. We estimate that in 2000 the aggregate risk of potentially severe reactions (excluding FNHTR and minor allergic reactions) was 43.2 per 100000 red cell units (95% confidence interval [CI]: 38.7-48.1), affecting 337 recipients, and 125.7 per 100000 platelet pools of 5 units (95% CI: 100.8-154.9), affecting 88 recipients. The most frequent potentially severe outcomes for red cell transfusion were hemolytic reactions and volume overload and for platelet transfusion were major allergic reactions and bacterial contamination. The current risk of human immunodeficiency virus and hepatitis C virus transmission is approximately 1 in 4 million and 1 in 3 million units, respectively. These estimates are useful for decisions concerning transfusion therapy, the informed consent process, and for evaluating efficacy of interventions to reduce risk.
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He Z, Zhuang H, Wang X, Song S, Dong Q, Yan J, Buehring GC, Luo G. Retrospective analysis of non-A-E hepatitis: possible role of hepatitis B and C virus infection. J Med Virol 2003; 69:59-65. [PMID: 12436478 DOI: 10.1002/jmv.10248] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
In an effort to determine the cause of non-A-E hepatitis, a retrospective study was undertaken on a group of patients with hepatitis but without serological infection markers of hepatitis viruses A-E. A total of 60 patients admitted to Beijing Ditan Hospital during the period of September 1997 and September 1999 were chosen for this study. These patients were diagnosed as either acute or chronic hepatitis, but no serological markers of hepatitis viruses A-E were detected. Since TT virus (TTV), human parvovirus B19 (B19), SEN virus (SENV), and GB virus C/HGV were reported to be associated with hepatitis, attempts were made to detect the presence of these viruses in the sera of patients with non-A-E hepatitis by a nested polymerase chain reaction (nPCR) method. Also, more sensitive nPCR and RT-nPCR methods were used to determine HBV DNA and HCV RNA in these patients. Results derived from these analyses demonstrate that HBV DNA was detected in most of these patients (47/60, 78.3%), suggesting that HBV infection played a major role in occult non-A-E hepatitis and detection of HBV DNA by more sensitive PCR methods such as nPCR should be considered for diagnosis of HBV infection. In addition, HCV RNA was detected in three (5%) of these patients. However, GBV-C (HGV) RNA was not detected, and TTV, B19, and SENV appear not to be associated with non-A-E hepatitis, as the prevalence rates of these viruses in patients with non-A-E hepatitis were similar to those in patients with viral hepatitis A-E. The results from this study indicate that co-infection of TTV or B19 with HBV did not increase the severity of the disease.
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Affiliation(s)
- Zhongping He
- Research Center of Virology, Beijing Ditan Hospital, Beijing, China.
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Abstract
For more than 40 years in the history of transfusion medicine, transmission of viral hepatitis from infected donors to recipients has been a frequent and serious adverse effect of the administration of blood components and plasma derivatives. This epidemic is now over, at least in developed and resource-rich countries. Hence, the attention of clinicians and investigators now focuses mainly on the measures to reduce the residual risk, on the possible emergence of novel or undiscovered agents causing post-transfusion hepatitis, and on the long-term outcome of patients who became infected more than ten years ago. The present article reviews these issues.
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Affiliation(s)
- D Prati
- Blood Transfusion and Transplantation Immunology Centre, Postgraduate School of Gastroenetrology, IRCCS Ospedale Maggiore, University of Milan, Italy.
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15
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Abstract
PURPOSE OF THE REVIEW The list of possible hepatotropic viruses continues to grow with the discovery of the GB virus-C, the TT virus and the SEN virus. There is emerging data on the biology of these newly discovered :In spite of continuing research into the pathogenicity of the GB virus-C and the TT virus, definite evidence linking them to acute or chronic liver disease is lacking. The SEN virus was reported in 2000, and although there seems to be an association between virus and transfusion-related hepatitis, more data are awaited before definite conclusions can be drawn. The effect of GB virus-C, the TT virus and the SEN virus co-infection on other viral and non-viral hepatitides has also been studied in some detail. Again, there is no definite evidence so far that these viruses modify other liver diseases. SUMMARY At the present time, diagnostic testing for these viruses does not seem to be warranted outside of clinical studies. The discovery of these viruses, however, paves the way for further research into novel viral agents that infect humans, other among hosts.
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Affiliation(s)
- K V Narayanan Menon
- Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA.
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16
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Abstract
The past decade has seen a consolidation of the safety measures built into the manufacture of coagulation factor concentrates for people with haemophilia. The scientific developments of the 1980s have been fully reflected in the manufacturing principles and the regulatory control of concentrate production, so that the safety of concentrate therapy now exceeds the safety of normal blood transfusion. A clear understanding of the epidemiology of the transfusion-transmitted viruses allows the selection of donors with a satisfactory safety profile. Source material for plasma-derived concentrates is now screened with sensitive tests that detect viral infection in donors at a very early phase in the viral life cycle. This decreases the potential viral load to levels that are easily eliminated by well-accredited viral inactivation procedures. These measures have ensured a high level of assurance regarding the safety of products from the traditional transfusion-transmitted infections. However, testing for some transfusion-transmitted viruses does not yet form part of mainstream blood screening; alternative strategies based upon the particular needs of pooled plasma product recipients may be more feasible. Whereas the risk of emerging pathogens has to be kept constantly under review, four such viruses identified over the 1990s have proven to be of little relevance to plasma product recipients and the need for measures specifically directed against them is debatable. The risk of variant Creuzfeldt-Jakob Disease (vCJD) is a special case of an emerging infection that is insufficiently well characterized to allow a conclusive assessment of its role in the safety of concentrates; however, data regarding the capacity of concentrate manufacturing methods to clear the putative agent are encouraging. The relative uncertainty surrounding vCJD has caused the influential regulatory authorities of North America to take a precautionary approach regarding the selection of blood donors. This is having an effect on the supply of factor VIII concentrates and has possibly affected the rate at which developed countries have switched to recombinant products. The safety of recombinant products continues to be supported through patient monitoring, and the new generation of plasma protein-free products will further enhance the role of these products as the treatment of choice with people with haemophilia. However, their cost-effectiveness relative to the current generation of plasma-derived products makes it unlikely that they will be accessible by developing countries. The dependence of most of the world's population of people with haemophilia on a safe and sufficient blood supply will therefore continue into the foreseeable future, and with it the need to maintain constant vigilance on blood safety matters.
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Affiliation(s)
- A Farrugia
- Manager Blood and Tissue Services, Therapeutic Goods Administration, Australian Commonwealth Department of Health and Aged Care, Adviser on Blood Safety, World Federation of Hemophilia, Australia.
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17
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Chamberland ME. Emerging infectious agents: do they pose a risk to the safety of transfused blood and blood products? Clin Infect Dis 2002; 34:797-805. [PMID: 11850862 DOI: 10.1086/338787] [Citation(s) in RCA: 41] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2001] [Revised: 11/02/2001] [Indexed: 11/03/2022] Open
Abstract
The blood supply is safer than it has been at any other time in recent history, and, in the context of other health care-related adverse events, the risks associated with blood transfusion are extremely small. The current high level of safety is the result of successive refinements and improvements in how blood is collected, tested, processed, and transfused; nonetheless, blood and plasma products remain vulnerable to newly identified or reemerging infections. In recent years, numerous infectious agents-including several newly discovered hepatitis viruses, the agents of transmissible spongiform encephalopathies, and tickborne pathogens-have been identified as potential threats to the safety of blood and plasma. Continued vigilance is critical to protect the blood supply from known pathogens and to monitor for the emergence of new infectious agents. Recent terrorist activities in the United States add new considerations to maintaining the safety and supply of blood. Education of clinicians and patients regarding the benefits and risks associated with the judicious use of blood and blood products can assist in informed decision making.
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Affiliation(s)
- Mary E Chamberland
- Centers for Disease Control and Prevention, National Center for Infectious Diseases, Division of Viral and Rickettsial Diseases, Atlanta, GA, 30333, USA.
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18
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Chu CM, Lin DY, Yeh CT, Sheen IS, Liaw YF. Epidemiological characteristics, risk factors, and clinical manifestations of acute non-A-E hepatitis. J Med Virol 2001; 65:296-300. [PMID: 11536236 DOI: 10.1002/jmv.2033] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
A substantial proportion of acute non-A, non-B hepatitis was of unknown etiology and was termed non-A-E hepatitis. Analysis of the clinical features is needed while attempting to identify the causative agent(s). In this study, the clinical and biochemical features of 53 patients who were admitted to hospital with acute non-A-E hepatitis were compared with a cohort of patients with acute hepatitis C (n = 70) and E (n = 5). In acute non-A-E hepatitis, the sex ratio was 34:19, and ages ranged from 21 to 76 years (median 49). Biochemical tests [median (range)] revealed albumin 3.6 (2.2-4.4) g/dl, AST 714 (193-2311) U/l, ALT 896 (310-3,000) U/l, bilirubin 11.2 (0.9-36.3) mg/dl, and prothrombin time > 1.1 (0-11.5) seconds. No patients reported parenteral exposures or household contact. Forty-five percent had severe hepatitis (i.e., albumin < 3 g/dl, bilirubin > 15 mg/dl or prothrombin time > 3 sec), including 3% with fulminant hepatitis. Chronic evolution was noted in 7%. These features were similar to those of hepatitis C or E, except for a significantly high frequency of parenteral exposures (20%), household contact (16%), and chronicity (70%) in hepatitis C. In conclusion, there is no obvious parenteral risk factor identified in acute non-A-E hepatitis. Clinical severity is similar to that of hepatitis C at least in hospitalized patients, but the rate of chronic evolution is much lower.
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Affiliation(s)
- C M Chu
- Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan.
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19
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Abstract
Following the development of tests for hepatitis C virus and hepatitis E virus infection, it became clear that there remained cases of hepatitis that were non-A-E. Such cases provided impetus for the search for additional hepatitis viruses and, by using molecular techniques, several candidates were identified. An enteric agent responsible for sporadic non-A and non-E hepatitis was tentatively called hepatitis F virus. However, the lack of any corroborating reports has cast doubt on its status as a true hepatitis virus. Two groups independently reported the isolation of a blood-borne virus, designated as hepatitis G virus (HGV) and GB virus C (GBV-C) by their respective discoverers. They were later shown to be isolates of the same virus. While the virus has a high prevalence in cases of non-A-E hepatitis, it also has a high prevalence in the appropriate control groups and convincing evidence for its replication in the liver is lacking. Another possible hepatitis virus, TT virus, was discovered in the blood of a patient with post-transfusion non-A-E hepatitis. By using PCR primers designed to overcome the high nucleotide sequence divergence, TT virus was found to be ubiquitous with a worldwide distribution. A disease association is thus unlikely. Most recently, a DNA virus designated as SEN-V has been announced as a major cause of non-A-E hepatitis. Based on limited data available to researchers, SEN-V is the most convincing contender for the new hepatitis virus title. However, the lessons learnt from the hepatitis virus pretenders will need to be applied to SEN-V and any future contenders.
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Affiliation(s)
- S Bowden
- Victorian Infectious Diseases Reference Laboratory, North Melbourne, Australia.
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20
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Abstract
TT virus (TTV) was cloned as a possible causative agent for non A to C posttransfusion hepatitis. Determination of the entire sequence of the virus revealed that the virus is the first human circovirus. The nucleotide sequence of TTV has a wide range of diversity and at least sixteen genotypes have been discovered to date. The prevalence of TTV infection in the normal population differs among countries, but exceeds 10% in several countries. Most of TTV infections are not associated with hepatitis, although there is evidence of TTV-induced hepatitis, especially caused by TTV of genotype I. To determine whether TTV is replicated in the liver is important in order to show that TTV is really a hepatitis virus, because results of a study in bone marrow transplant (BMT) recipients suggested that TTV might be replicated mainly in the hematopoietic cells. The prevalence of TTV infection in patients with hematological disorders who regularly require blood products was extremely high, but most of the infections did not cause liver injury, even in BMT recipients.
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Affiliation(s)
- Y Kanda
- Department of Cell Therapy and Transplantation Medicine, Faculty of Medicine, University of Tokyo, Japan
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21
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Tanaka Y, Hayashi J, Ariyama I, Furusyo N, Etoh Y, Kashiwagi S. Seroepidemiology of TT virus infection and relationship between genotype and liver damage. Dig Dis Sci 2000; 45:2214-20. [PMID: 11215742 DOI: 10.1023/a:1026644704220] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
TT virus (TTV) has been identified in patients with posttransfusion hepatitis of unknown etiology and is thought to be a new hepatitis virus. We determined the extent of TTV infection in the Japanese general population and the relationship between TTV DNA genotype and liver damage. In 1998, we tested 847 serum samples for TTV. TTV DNA was assayed by a nested polymerase chain reaction and classified into three different genotypes and eight subtypes. TTV DNA was detected in 25.3% and 32.4% of the inhabitants of the two areas studied, respectively. The genotype distribution was similar in both areas. G1, G2, and G3 were 60%, 20%, and 5%, respectively. Of the 20 subjects with TTV DNA alone and elevated serum ALT levels, 18 were G1, one was G2, and one was G3. TTV infection is endemic in the Japanese general population studied. The main TTV genotype, G1, may be related to the ensuing liver damage.
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Affiliation(s)
- Y Tanaka
- Department of General Medicine, Kyushu University Hospital, Fukuoka, Japan
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22
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23
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Cleavinger PJ, Persing DH, Li H, Moore SB, Charlton MR, Sievers C, Therneau TM, Zein NN. Prevalence of TT virus infection in blood donors with elevated ALT in the absence of known hepatitis markers. Am J Gastroenterol 2000; 95:772-6. [PMID: 10710073 DOI: 10.1111/j.1572-0241.2000.01820.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Recently a novel DNA virus (TT virus) has been identified in Japan and shown to be associated with elevated aminotransferase levels after blood transfusion. The exact role of TTV in the pathogenesis of liver disease is yet to be established. Our aim was to determine the prevalence and role of TTV in the pathogenesis of elevated transaminases in healthy blood donors in the absence of markers for viral hepatitis A-C. METHODS Stored sera were collected from 99 healthy blood donors with elevated alanine amino transferase (ALT) values that were discovered at the time of blood donation. A total of 146 samples were obtained from healthy donors with normal ALT values who were used as controls. None of the patients or controls had a history of blood transfusion or had clinical signs of acute or chronic hepatitis. Serological markers for hepatitis A, hepatitis B, and hepatitis C viruses were negative. TTV DNA was amplified and detected using polymerase chain reaction followed by gel electrophoresis. RESULTS Five of 99 (5%) samples obtained from donors with elevated ALT had TTV DNA detected by PCR, as compared to one of 146 (0.7%) of those with normal ALT (p = 0.006). Among those with elevated ALT, mean ALT values in patients with TTV (296 +/- 305 U/L) were higher than in patients without TTV (95 +/- 37 U/L), but the difference was not statistically significant (p = 0.08). The two samples with highest ALT values (both >450 U/L) were among the five samples with detectable TTV DNA in serum. CONCLUSIONS Although TTV is not likely to explain the majority of elevated ALT cases in otherwise healthy blood donors, TTV infection may potentially be associated with some cases. Based on these findings, we propose that the role of TTV in the pathogenesis of acute and chronic liver diseases merits further investigation.
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Affiliation(s)
- P J Cleavinger
- Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
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24
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Abstract
The list of potential hepatotrophic viruses continues to grow, with the recent discovery of the GB virus-C, the TT virus, and the SEN virus. Prevalence rates of the GB virus-C have ranged from 1.2% to 13% among healthy blood donors from all over the world. Higher prevalence rates have been reported among intravenous drug users. Similarly, the TT virus has a global distribution. However, in spite of numerous reports of the presence of both of these viruses in various kinds of liver diseases, definite evidence linking it to a specific disease or illness is lacking. The SEN virus is thought to be a novel viral agent that may be linked to cryptogenic chronic hepatitis, but data are awaited.
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Affiliation(s)
- K V Menon
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA
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25
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Handajani R, Lusida MI, Suryohudoyo P, Adi P, Setiawan PB, Nidom CA, Soemarto R, Katayama Y, Fujii M, Hotta H. Prevalence of GB virus C/Hepatitis G virus infection among various populations in Surabaya, Indonesia, and identification of novel groups of sequence variants. J Clin Microbiol 2000; 38:662-8. [PMID: 10655364 PMCID: PMC86171 DOI: 10.1128/jcm.38.2.662-668.2000] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
A molecular epidemiological study was performed to investigate the prevalence of GB virus C/hepatitis G virus (GBV-C/HGV) infection among various populations in Surabaya, Indonesia. The prevalence of GBV-C/HGV RNA, determined by reverse transcription-PCR for a portion of the NS3 region of the viral genome, was 2.7% (4 of 150) among randomly collected blood donor sera, which were all negative for both hepatitis B virus surface antigen and antibodies against hepatitis C virus (HCV). On the other hand, the prevalence among anti-HCV-positive blood donors was 17.8% (13 of 73), with the ratio being significantly higher than that observed with the anti-HCV-negative blood donors (P < 0.001). A high prevalence of GBV-C/HGV infection was also observed among patients with chronic liver disease, such as chronic hepatitis (5.7%), liver cirrhosis (11. 5%), and hepatocellular carcinoma (7.0%), and patients on maintenance hemodialysis (29.0%). No correlation was observed between GBV-C/HGV viremia and serum alanine aminotransferase levels in the populations tested, suggesting the possibility that GBV-C/HGV does not cause apparent liver injury. Phylogenetic analysis of sequences of a portion of the 5' untranslated region and the E1 region of the viral genome identified, in addition to a previously reported then novel group of GBV-C/HGV variants (group 4), another novel group of variants (group 5). This result suggests that GBV-C/HGV can be classified into at least five genetic groups. GBV-C/HGV isolates of group 4 and group 5 were each shown to comprise approximately 40% of the total Indonesian isolates.
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Affiliation(s)
- R Handajani
- Departments of Biochemistry, Faculty of Medicine, Airlangga University, Surabaya, Indonesia
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26
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Bradley DW. Studies of non-A, non-B hepatitis and characterization of the hepatitis C virus in chimpanzees. Curr Top Microbiol Immunol 1999; 242:1-23. [PMID: 10592653 DOI: 10.1007/978-3-642-59605-6_1] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/18/2023]
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27
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Mason AL. TT virus: will work for food? Am J Gastroenterol 1999; 94:3398-401. [PMID: 10606288 DOI: 10.1111/j.1572-0241.1999.01658.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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28
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Colombatto P, Brunetto MR, Kansopon J, Oliveri F, Maina A, Aragon U, Bortoli ML, Scatena F, Baicchi U, Houghton M, Bonino F, Weiner AJ. High prevalence of G1 and G2 TT-virus infection in subjects with high and low blood exposure risk: identification of G4 isolates in Italy. J Hepatol 1999; 31:990-6. [PMID: 10604571 DOI: 10.1016/s0168-8278(99)80310-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Abstract
BACKGROUND/AIMS A non-enveloped single-stranded DNA virus (TTV) was detected in Japanese patients with fulminant hepatitis (47%) and chronic liver disease of unknown etiology (46%) more frequently than in blood donors (12%). Subsequent studies, however, questioned the association of TTV with liver disease. We further investigated the role of this novel virus in liver diseases. METHODS We tested 106 patients and 102 blood donors for TTV by polymerase chain reaction using conserved region primers. RESULTS TTV DNA was found in 19 of 102 volunteer blood donors (18.6%) and in 27 of 106 patients with liver disease (25.5%): 10 of 28 chronic hepatitis B (35.7%), 9 of 28 chronic hepatitis C (32.1%) and 8 of 50 (16%) cryptogenic liver disease patients. Previous interferon treatment was not associated with a significantly lower prevalence of TTV infection. TTV prevalence was higher in patients with blood exposure (42.8%, 6/14) than in patients without risk factors (21.4%, 18/84). Four of five patients (80%) with HBV familial infection and without blood exposure were also TTV positive. Partial nucleotide sequences from 3 Italian isolates diverged more than 30% from the 2 prototype genotypes G1 and G2 and were 88% homologous to the recently described genotype G4. CONCLUSIONS G1 and G2 TTV are common in Italy and in the USA in liver disease patients and in blood donors. The prevalence is high in patients with blood exposure but also in subjects without risk factors; other routes of transmission should therefore be considered.
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Affiliation(s)
- P Colombatto
- Gastroenterology and Hepatology Unit, Spedali Riuniti Santa Chiara, Azienda Ospedaliera Pisana, Cisanello, Pisa, Italy
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29
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Sathar MA, Soni PN, Pegoraro R, Simmonds P, Smith DB, Dhillon AP, Dusheiko GM. A new variant of GB virus C/hepatitis G virus (GBV-C/HGV) from South Africa. Virus Res 1999; 64:151-60. [PMID: 10518711 DOI: 10.1016/s0168-1702(99)00090-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Phylogenetic analysis of the 5' non-coding region (5'NCR) sequences has demonstrated that GB virus C/hepatitis G virus (GBV-C/HGV) can be separated into three major groups that correlate with the geographic origin of the isolate. Sequence analysis of the 5'NCR of 54 GBV-C/HGV isolates from 31 blood donors, 11 haemodialysis patients and 12 patients with chronic liver disease suggests the presence of a new variant of GBV-C/HGV in the province of KwaZulu Natal, South Africa. Eleven isolates grouped as group 1 variants (bootstrap support, 90%) found predominantly in West and Central Africa, a further six isolates grouped as group 2 variants (bootstrap support, 58%) found in Europe and North America; five of which grouped as 2a (bootstrap support, 91%) and one as 2b (bootstrap support, 87%), the latter also includes isolates from Japan, East Africa and Pakistan. Although the remaining 37 GBV-C/HGV isolates were more closely related to group 1 variants (bootstrap support, 90%), they formed a cluster, which was distinct from all other known GBV-C/HGV sequences. None of the South African isolates grouped with group 3 variants described from Southeast Asia. Three variants of GBV-C/HGV exist in KwaZulu Natal: groups 1, 2 and a new variant, which is distinct from other African isolates.
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Affiliation(s)
- M A Sathar
- Department of Medicine, University of Natal/King Edward VIII Hospital, South Africa.
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30
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Ding X, Mizokami M, Kang LY, Cao K, Orito E, Tanaka Y, Ueda R, Sasaki M. Prevalence of TT virus and GBV-C infections among patients with liver diseases and the general population in Shanghai, China. Virus Genes 1999; 19:51-8. [PMID: 10499450 DOI: 10.1023/a:1008188623062] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
To determine the prevalence of TT virus (TTV) and GB virus C/hepatitis G virus (GBV-C) infections among patients with liver disease and the general population in Shanghai, China, we studied 90 patients with liver diseases (acute hepatitis, 28; chronic hepatitis, 27; liver cirrhosis, 20; hepatocellular carcinoma, 15) and 90 age, sex matched healthy blood donors as controls. There were no significant differences in the clinical and demographic characteristics between the two groups, except for liver function test values. There was a statistical difference between the patient group and the control group with regard to the prevalence of TTV DNA (23.5% in patient group, 11.1% in control group, P < 0.05), although no differences in clinical features could be found between TTV DNA-positive and negative subjects. Also, no differences in TTV DNA prevalence among various categories of liver diseases were noted (P = NS). The prevalence of HBsAg was significantly different between the patient group (36.7%) and the control group (3.3%) (P0.01), whereas the prevalence of anti-HCV and GBV-C RNA were not significantly different between the two groups. The nucleotide sequences were determined in the TTV DNA-positive samples and evaluated using phylogenetic analysis which suggested that they could be divided into two main genotypes designated as genotype 1 and 2. There were five samples clustered into 3 hitherto unknown subtypes of genotype 2. We concluded that (1) although TTV infection is widespread among both groups and there is a statistical difference of TTV infection between them, no hepatic damaging evidence and correlation with certain liver disease could be found in this study, suggest that TTV may not be major cause of liver disease, (2) GBV-C infection is frequent, but the virus is not the cause of liver diseases, and (3) new subtypes of TTV may exist in Shanghai, China.
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Affiliation(s)
- X Ding
- Second Department of Medicine, Nagoya City University Medical School, Nagoya, Japan
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31
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Okamoto H, Nishizawa T, Ukita M, Takahashi M, Fukuda M, Iizuka H, Miyakawa Y, Mayumi M. The entire nucleotide sequence of a TT virus isolate from the United States (TUS01): comparison with reported isolates and phylogenetic analysis. Virology 1999; 259:437-48. [PMID: 10388667 DOI: 10.1006/viro.1999.9769] [Citation(s) in RCA: 94] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
A nonenveloped and single-stranded DNA virus designated TT virus (TTV) has been reported from Japan in association with hepatitis of unknown etiology. Very recently, the prototype TTV isolate (TA278) of genotype 1 is proven to have a circular genome with 3852 nucleotides. A TTV isolate (TUS01) was recovered from a blood donor in the United States, and its entire circular nucleotide sequence of 3818 nucleotides was determined. It possessed two open reading frames coding for 761 and 156 amino acids, respectively. TUS01 shared 60.5% of the nucleotide sequence with the TA278 isolate from Japan that was longer by 35 nt. The sequence of the noncoding region of 1203 nt was conserved with a similarity of 83.4%. Sequence preservation was much lower for the two open reading frames; nucleotide and amino acid sequences were 54.8 and 37.0% similar, respectively, for one and 55.5 and 38.8% similar for the other. By comparison of a partial sequence of 222 nucleotides among 239 TTV isolates available from various countries, at least 11 genotypes with sequence divergence of >30% were recognized. TUS01 was deduced to be of genotype 11, which has not been reported before. Conserved sequences in the noncoding region could be used as primers for sensitively detecting TTV DNA by polymerase chain reaction. Divergent sequences in coding regions would be useful as primers for distinguishing various TTV genotypes.
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Affiliation(s)
- H Okamoto
- Immunology Division and Division of Molecular Virology, Jichi Medical School, Tochigi-Ken, 329-0498, Japan
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32
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Akahane Y, Sakamoto M, Miyazaki Y, Okada S, Inoue T, Ukita M, Okamoto H, Miyakawa Y, Mayumi M. Effect of interferon on a nonenveloped DNA virus (TT virus) associated with acute and chronic hepatitis of unknown etiology. J Med Virol 1999; 58:196-200. [PMID: 10447412 DOI: 10.1002/(sici)1096-9071(199907)58:3<196::aid-jmv2>3.0.co;2-l] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
An unenveloped DNA virus named TT virus (TTV) has been reported in association with acute and chronic hepatitis of unknown etiology. The effect of interferon on TTV was evaluated in the patients with chronic hepatitis C who were coinfected with TTV. TTV DNA was determined by a polymerase chain reaction with heminested primers in the 96 patients with chronic hepatitis C who received interferon-alpha (516 million units in 26 weeks) and followed for 24 months thereafter. TTV DNA was detected in 31 (32%) patients before therapy. TTV DNA became undetectable during interferon therapy and remained absent in 14 (45% of the 31 patients) through 24 months thereafter. The four patients with pretreatment TTV DNA titer > or =10(3)/ml did not respond. These results indicate that TTV is sensitive to interferon, and the response would be inversely correlated with pretreatment viral titers.
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Affiliation(s)
- Y Akahane
- First Department of Internal Medicine, Yamanashi Medical University, Japan
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33
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Paraná R, Vitvitski L, Andrade Z, Trepo C, Cotrim H, Bertillon P, Silva F, Silva L, de Oliveira IR, Lyra L. Acute sporadic non-A, non-B hepatitis in Northeastern Brazil: etiology and natural history. Hepatology 1999; 30:289-93. [PMID: 10385669 DOI: 10.1002/hep.510300143] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
In a 4-year follow-up study, patients with acute sporadic non-A, non-B (NANB) hepatitis were evaluated to determine the etiology and natural history of the disease. Acute hepatitis C virus (HCV) was detected in 13 of 43 (30%) of patients, anti-hepatitis E virus (HEV) IgG in 5 (12%), and 25 (58%) were considered non-A-E. The HCV RNA was detected in all HCV patients but none of the non-A-E cases. The initial clinical and biochemical presentation of the HCV and non-A-E cases was quite similar, although 2 of the non-A-E patients had severe disease. The 5 patients who were found to be anti-HEV IgG-reactive recovered within 6 months of follow-up. Of the 13 HCV cases, alanine transaminase (ALT) levels returned to normal in 7 (53. 8%), while 6 (46.2%) continued to show abnormal ALT after 6 months of follow-up. However, 9 (69.2%) of them remained HCV-RNA-positive, denoting virological/biochemical dissociation. Long-term follow-up showed a reappearance of HCV RNA in 2 of the 4 patients who were in virological remission performing 84% of chronicity rate. Acute non-A-E hepatitis patients were less likely to evolve toward chronicity, as compared with acute HCV cases (16% vs. 84%; P =.0001). Only 4 (16%) of the non-A-E patients were hepatitis G virus (HGV)-RNA-positive. Concerning risk factors for acquiring parenterally transmitted viruses, tattooing was the only one that could be associated with HCV transmission (P =.002). No risk factors could be identified for putative non-A-E virus transmission. Liver biopsies performed for chronic HCV patients showed a variable degree of inflammation, while the non-A-E patients presented less severe histological disease.
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Affiliation(s)
- R Paraná
- Hepatology Unit of Bahia, University Hospital of Bahía, Brazil
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Hsieh SY, Wu YH, Ho YP, Tsao KC, Yeh CT, Liaw YF. High prevalence of TT virus infection in healthy children and adults and in patients with liver disease in Taiwan. J Clin Microbiol 1999; 37:1829-31. [PMID: 10325332 PMCID: PMC84962 DOI: 10.1128/jcm.37.6.1829-1831.1999] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
A newly identified DNA virus, named TT virus (TTV), was found to be related to transfusion-associated hepatitis. We conducted the following experiments to evaluate its pathogenic role in liver disease and potential modes of transmission. We used PCR to detect TTV DNA in serum. The rates of TTV viremia in 13 patients with idiopathic acute hepatitis, 14 patients with idiopathic fulminant hepatitis, 22 patients with chronic hepatitis, and 19 patients with cirrhosis of the liver were 46, 64, 55, and 63%, respectively, and were not significantly different from those in 50 healthy control subjects (53%). PCR products derived from seven patients with liver disease and three healthy controls were cloned and then subjected to phylogenetic analyses, which failed to link a virulent strain of TTV to severe liver disease. TTV infection was further assessed in an additional 148 subjects with normal liver biochemical tests, including 30 newborns (sera collected from the umbilical cord), 23 infants, 16 preschool children, 21 individuals of an age prior to that of sexual experience (aged 6 to 15 years), 15 young adults (aged under 30 years), and 43 individuals older than 30 years. The rates of TTV viremia were 0, 17, 25, 33, 47, and 54%, respectively. These findings suggest that TTV is transmitted mainly via nonparenteral daily contact and frequently occurs very early in life and that TTV infection does not have a significant effect on liver disease.
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Affiliation(s)
- S Y Hsieh
- Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Republic of Taiwan.
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Giménez-Barcons M, Forns X, Ampurdanés S, Guilera M, Soler M, Soguero C, Sánchez-Fueyo A, Mas A, Bruix J, Sánchez-Tapias JM, Rodés J, Saiz JC. Infection with a novel human DNA virus (TTV) has no pathogenic significance in patients with liver diseases. J Hepatol 1999; 30:1028-34. [PMID: 10406180 DOI: 10.1016/s0168-8278(99)80256-6] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND/AIMS A recently identified DNA virus, termed TT virus (TTV), has been associated with post-transfusional hepatitis, and a high prevalence of TTV infection in patients with acute or chronic liver disease of unknown etiology has been reported from Japan, but few data are available about TTV infection in other countries. METHODS Using hemi-nested-PCR amplification to detect TTV-DNA sequences in serum, we investigated TTV infection in blood donors and in patients with liver diseases of varied etiology. RESULTS The prevalence of TTV infection was 13.7% in blood donors (23/168), 18.6% in chronic hepatitis C (19/102), 28.6% in chronic hepatitis B (16/56), 29.9% in hepatocellular carcinoma (20/67), 9.1% in cryptogenic chronic liver disease (2/22) and 39.6% in fulminant hepatitis (19/48). The prevalence of TTV infection in patients with virus-induced or idiopathic fulminant hepatitis was similar. Comparison of TTV-infected and non-infected patients did not reveal significant differences concerning demographic, epidemiological or histopathological features. In patients with hepatitis C, response to interferon therapy was not related to TTV infection. Phylogenetic analysis of TTV isolates showed that at least three different types of TTV are present in Spain. CONCLUSIONS Our data suggest that TTV infection is frequent among blood donors and patients with acute liver disease. However, pathogenic effects associated with TTV infection were not observed.
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Affiliation(s)
- M Giménez-Barcons
- Department of Medicine, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, University of Barcelona, Spain
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Itoh K, Hirakawa K, Okamoto H, Ukita M, Tanaka H, Sawada N, Tsuda F, Miyakawa Y, Mayumi M. Infection by an unenveloped DNA virus associated with non-A to -G hepatitis in Japanese blood donors with or without elevated ALT levels. Transfusion 1999; 39:522-6. [PMID: 10336003 DOI: 10.1046/j.1537-2995.1999.39050522.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND An unenveloped, single-stranded DNA virus named TT virus has been found in association with elevated alanine aminotransferase (ALT) levels in recipients of transfusions and has been detected frequently in patients with acute or chronic hepatitis of non-A to -G etiology in Japan. DNA of the TT virus was searched for in blood donors with or without elevated ALT levels. STUDY DESIGN AND METHODS A total of 861 blood donors without previous transfusions and who were negative for markers of hepatitis B or C virus infection were tested. DNA of the TT virus was detected by polymerize chain reaction with hemi-nested primers. RESULTS TT virus DNA was detected in 62 of 280 (22.1% [95% CI: 18.1-26.6]) donors with elevated ALT levels (mean +/- SD, 89.3 +/- 36.4 U/L; range, 61-301 U/L), which is significantly more frequently (p<0.02) than its detection in 91 of 581 (15.7% [95% CI: 13.2-18.4]) donors with normal ALT (< or = 45 U/L). The frequency of TT virus DNA increased with age, in donors with and without elevated ALT. CONCLUSION The detection of TT virus DNA, at a frequency higher in donors with elevated ALT than in those without, strengthens the association of TT virus with non-A to -G hepatitis.
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Affiliation(s)
- K Itoh
- Japanese Red Cross Yamaguchi Blood Center, Yamaguchi
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37
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Kato H, Mizokami M, Nakano T, Kondo Y, Dashnyam B, Oyunsuren T, Ueda R. High prevalence and phylogenetic analysis of TT-virus infection in Mongolia. Virus Res 1999; 60:171-9. [PMID: 10392725 DOI: 10.1016/s0168-1702(99)00016-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
A novel DNA virus, TT-virus (TTV), was isolated from a post-transfusion hepatitis patient in Japan. The prevalence of TTV infection was investigated among patients with chronic liver disease and normal alanine aminotransferase (ALT) volunteers as controls in Mongolia. Polymerase chain reaction (PCR) was employed to detect TTV DNA using specific primers derived from open reading frame 1 (ORF1) of the TTV genome. Nucleotide sequences of samples positive for TTV DNA were determined. The sequences were analyzed by a molecular evolutionary method. Fifty (60.2%) hepatitis patients and 12 (42.9%) volunteers were positive for TTV DNA. The serum ALT levels did not differ significantly between patients with single TTV infection and without TTV, HBV and HCV infection. Similarly, the serum ALT levels did not differ significantly between controls with and without TTV infection. Dual infection of TTV with either HBV or HCV did not affect the ALT levels of hepatitis patients. The molecular evolutionary tree showed that TTV was a heterogeneous virus and all strains could be divided into three genotypes in Mongolia. A new genotype was identified that was distinct from those previously reported.
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Affiliation(s)
- H Kato
- Second Department of Medicine, Nagoya City University Medical School, Kawasumi, Japan
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38
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Okamoto H, Kato N, Iizuka H, Tsuda F, Miyakawa Y, Mayumi M. Distinct genotypes of a nonenveloped DNA virus associated with posttransfusion non-A to G hepatitis (TT virus) in plasma and peripheral blood mononuclear cells. J Med Virol 1999; 57:252-8. [PMID: 10022796 DOI: 10.1002/(sici)1096-9071(199903)57:3<252::aid-jmv7>3.0.co;2-q] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
TT virus (TTV) is a nonenveloped, single-stranded DNA virus with little sequence homology to known viruses, and associated with elevated transaminase levels in the patients with posttransfusion hepatitis of unknown etiology. The DNA of TTV was detected, by semi-nested polymerase chain reaction, in peripheral blood mononuclear cells (PBMC) from the 30 healthy individuals with circulating virus in plasma. A sequence of 222 bases was determined on 6-10 TTV DNA clones each from plasma and 6 clones -each from PBMC from eight individuals selected at random from this group. TTV can be classified into genotypes separated by an evolutionary distance > 0.30, which can be divided further into subtypes separated by that of 0.15. Three individuals possessed two different TTV variants of distinct genotypes, with predominant genotypes different between plasma and PBMC. Another possessed TTV of the same genotype in both the plasma and PBMC, but clones with a subtype not seen in plasma were observed in PBMC. A third individual had TTV variants with or without a deletion mutation, and those with the deletion mutation abounded only in PBMC. The remaining three individuals were infected with TTV with the same sequence both in plasma and PBMC. These results indicate that TTV variants with phylogenetic differences could infect the same individual, and that some variants would have a predilection for PBMC. It remains to be seen, however, if TTV replicates in PBMC or whether it has been sequestered before its evolution in the host.
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Affiliation(s)
- H Okamoto
- Immunology Division, Jichi Medical School, Tochigi-Ken, Japan
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39
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Ikeda H, Takasu M, Inoue K, Okamoto H, Miyakawa Y, Mayumi M. Infection with an unenveloped DNA virus (TTV) in patients with acute or chronic liver disease of unknown etiology and in those positive for hepatitis C virus RNA. J Hepatol 1999; 30:205-12. [PMID: 10068097 DOI: 10.1016/s0168-8278(99)80063-4] [Citation(s) in RCA: 70] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND/AIMS An unenveloped single-stranded DNA virus (TTV) has been reported in association with elevated transaminase levels in patients with posttransfusion hepatitis and in those with acute or chronic liver disease of unknown etiology. To further evaluate the association of TTV with liver disease, TTV DNA was searched for in patients with acute or chronic liver disease of various etiologies. METHODS TTV DNA was determined by polymerase chain reaction with hemi-nested primers in 64 patients with acute or chronic liver disease of unknown etiology and in 100 with acute or chronic liver disease positive for antibody to hepatitis C virus (HCV) as well as HCV RNA. RESULTS TTV DNA was detected in two of the seven (29%) patients with acute hepatitis of unknown etiology, but in none of the four patients with acute HCV-associated hepatitis. It was detected in 27 of the 57 (47%) patients with chronic liver disease of unknown etiology at a frequency significantly higher (p<0.001) than that in 17 of the 96 (18%) patients with chronic HCV-associated liver disease. By contrast, RNA of hepatitis G virus was detected in none of the patients with acute hepatitis, and only in one of the 57 (2%) patients with chronic liver disease of unknown etiology as well as in six of the 96 (6%) patients with chronic HCV-associated liver disease. CONCLUSIONS Based on the obtained results, TTV has a role in the development of acute and chronic liver disease of unknown etiology.
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Affiliation(s)
- H Ikeda
- Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
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40
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Ling BH, Zhuang H, Cui YH, An WF, Li ZJ, Wang SP, Zhu WF. A cross-sectional study on HGV infection in a rural population. World J Gastroenterol 1998; 4:489-492. [PMID: 11819351 PMCID: PMC4723435 DOI: 10.3748/wjg.v4.i6.489] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the epidemiological characteristics and clinical significance of HGV infection, and to compare with HBV and HCV infections.
METHODS: Anti-HGV, HBsAg, anti-HBs, anti-HBc and anti-HCV were detected by enzyme-linked immunoassys (EIA). Anti-HGV positive sera were further tested for HGV RNA by a nested reverse transcription polymerase chain reaction (RT-nPCR).
RESULTS: The anti-HGV prevalence rate was 12.9% in the rural population. It was relatively low in children under 10 years of age, and then increased with age and peaked in the group of 50-59 years (29.2%). The Carrier rate of HBsAg was 12.6% in the population and quickly reached the highest (16.2%) in the 5-year age group. The prevalence rate of HBV infection was 64.9%, and rose to a high level in the group of 10 years, and maintained high till up to the top of 79.2% in the 50-59 age group. The HCV infection rate was 15.3%. No Anti-HCV positive cases were found in the group under 10 years of age. It was particularly high in the 20-40 age group, and reached the peak in the group of 30 years old. No significant differences were found in the infection rates of HBV, HCV and HGV between male and female. HGV infection was associated with the history of blood donation and the sexual transmission. The anti-HGV positive rate in wives of husbands with HGV infection was 53.3%, significantly higher than that in those with anti-HGV negative husbands (7.8%). HGV coinfection with HBV or HCV had no influence on serum alanine aminotransferase (ALT). No ALT elevation was found in the group with HGV infection alone.
CONCLUSION: The epidemiological characteristics of HGV infection are different from that of HBV and HCV. HGV is transmitted by blood and sex, and does not seem to cause liver damage.
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41
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Silini E, Belli L, Alberti AB, Asti M, Cerino A, Bissolati M, Rondinara G, De Carlis L, Forti D, Mondelli MU, Ideo G. HGV/GBV-C infection in liver transplant recipients: antibodies to the viral E2 envelope glycoprotein protect from de novo infection. J Hepatol 1998; 29:533-40. [PMID: 9824261 DOI: 10.1016/s0168-8278(98)80147-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND/AIMS Liver transplantation for endstage liver cirrhosis provides a useful model to investigate the pathogenetic role of hepatotropic viral agents. Recently, a new member of the Flaviviridae family, provisionally named HGV/GBV-C virus, has been associated with acute and chronic non A-E hepatitis. We studied 136 patients with cirrhosis consecutively transplanted at our institution for evidence of hepatitis G virus infection and correlation with the patients' clinical course. METHODS All patients survived for at least 6 months after transplantation (median follow-up 44 months) and underwent routine liver biopsies. Hepatitis G virus infection was studied using both direct viral RNA identification by RT-PCR and indirect detection of antibodies to the E2 glycoprotein. RESULTS There was a high frequency of the hepatitis G virus among patients undergoing liver transplantation, with HGV RNA and anti-E2 prevalence rates of 18.4% and 26.5%, respectively. HGV RNA prevalences significantly increased after transplantation (47.8%), with 47.3% rate of new infections in susceptible subjects. Anti-E2 antibodies were significantly more prevalent among patients transplanted for HCV-related cirrhosis and represented a strong protective factor against hepatitis G virus reinfection or recurrent infection. No correlation was found between HGV RNA or anti-E2 prevalences and survival after transplantation or rates of recurrent liver damage. CONCLUSIONS All available evidence suggests that, although liver transplant patients are heavily exposed to hepatitis G virus both before and after transplantation, hepatitis G virus does not induce liver disease in this setting. Most infections appear to be self-limited and induce a protective immunity which is marked by the presence of anti-E2 antibodies.
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Affiliation(s)
- E Silini
- Department of Pathology and Infectious Diseases, University of Pavia and IRCCS Policlinico S. Matteo, Italy
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42
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Naoumov NV, Petrova EP, Thomas MG, Williams R. Presence of a newly described human DNA virus (TTV) in patients with liver disease. Lancet 1998; 352:195-7. [PMID: 9683209 DOI: 10.1016/s0140-6736(98)04069-0] [Citation(s) in RCA: 232] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND A newly described DNA virus, named transfusion-transmitted virus (TTV), was recently detected with high prevalence in Japanese patients with fulminant hepatitis and chronic liver disease of unknown aetiology. We investigated the presence of this virus in patients with liver disease in the UK to find out whether TTV infection is associated with liver damage. METHODS We used semi-nested PCR to amplify TTV DNA from serum samples from 126 adults, of whom 72 were patients with a range of chronic liver diseases, 24 had spontaneous resolution of infection with hepatitis C virus (HCV), and 30 were normal controls. Direct DNA sequencing and phylogenetic analysis were used to characterise the TTV isolates. FINDINGS We detected TTV DNA in 18 (25%) of the 72 patients with chronic liver disease, which was not different from the 10% prevalence in normal controls (p=0.15). The rate of TTV DNA was similar among patients with various liver diseases. The majority of TTV-positive cases had no biochemical or histological evidence of significant liver damage. TTV DNA sequencing of nine isolates showed the same genotypic groups as in Japan: three patients were infected with genotype 1, which showed 4% nucleotide divergence, and six patients were infected with genotype 2 with 15-27% divergence. INTERPRETATION The high prevalence of active TTV infection in the general population, both in the UK and in Japan, and the lack of significant liver damage, suggest that TTV, similar to hepatitis G virus (HGV), may be an example of a human virus with no clear disease association.
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Affiliation(s)
- N V Naoumov
- Institute of Hepatology, Department of Medicine, University College London Medical School, UK.
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43
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Sobue S, Higashi K, Nakao H, Takahashi Y, Itoh M, Nakajima K. Hepatitis G virus infection in patients with alcoholic liver disease. Alcohol Clin Exp Res 1998; 22:156S-160S. [PMID: 9622395 DOI: 10.1111/acer.1998.22.s3_part1.156s] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The recently discovered hepatitis G virus (HGV) is believed to be a single-stranded RNA virus belonging to the Flaviviridae family, similar to hepatitis C virus (HCV), but much remains to be learned about its characteristics and clinical manifestations. Although it has been suggested that alcohol intake might have an effect on liver pathology by promoting the proliferation of HCV, the association between HGV infection and alcohol intake is yet to be elucidated. In the present study, we investigated the prevalence of HGV-RNA and HCV-RNA in 63 patients with alcoholic liver disease, and studied the effects of alcohol on the progression of hepatic damage in HGV-RNA positive patients. Among these 63 patients, 9 (14%) were HGV-RNA-positive and 37 (59%) were HCV-RNA-positive. Seven (78%) of the nine HGV-RNA positive patients were also infected with HCV. The patients showed no significant differences of clinical features in relation to the presence or absence of HGV infection. There were also no differences of liver histology among HCV-RNA-positive patients with or without HGV-RNA. The two patients infected with HGV alone had alcoholic hepatitis and nonspecific reactive hepatitis, respectively. In this study, alcohol seemed to have little influence on the progression of the liver histology in HGV-RNA-positive patients.
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Affiliation(s)
- S Sobue
- First Department of Internal Medicine, Medical School, Nagoya City University, Nagoya, Japan
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44
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Tanaka E, Kiyosawa K, Shimoda K, Hino K, Tacke M, Schmolke S, Engel AM, Hess G. Evolution of hepatitis G virus infection and antibody response to envelope protein in patients with transfusion-associated non-A, non-B hepatitis. J Viral Hepat 1998; 5:153-9. [PMID: 9658367 DOI: 10.1046/j.1365-2893.1998.00095.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
The clinical significance and course of acute hepatitis G virus (HGV) infection were studied by measuring HGV RNA and antibody to HGV envelope protein E2 (HGV-E2 antibody). A total of 59 patients with transfusion-associated non-A, non-B hepatitis, who were followed-up for more than 1 year, were selected retrospectively. HGV RNA was measured by reverse transcriptase (RT) and nested polymerase chain reaction (PCR) was performed, using primer sets, in the 5'-non-coding region of the HGV genome. HGV-E2 antibody was measured by enzyme-linked immunosorbent assay (ELISA) using recombinant E2 protein. Of the 59 patients, 51 (86%) were infected with hepatitis C virus (HCV) and 12 (20%) were infected with HGV; 11 of the 12 with HGV infection were also infected with HCV. HGV viraemia was cleared during the follow-up period in seven of the 12 patients with HGV infection. All these seven patients seroconverted for HGV-E2 antibody just before or just after the clearance of HGV viraemia. In contrast, all five patients without clearance of HGV viraemia were negative for HGV-E2 antibody (P = 0.0013). Of seven patients with continuous HGV viraemia at 1 year from the onset of acute hepatitis, four with HCV RNA showed chronic elevation of alanine aminotransferase (ALT) but three without HCV RNA did not. The severity of acute hepatitis was similar between patients with both HGV and HCV infections and in those with HCV infection alone. The majority of patients with HGV infection cleared the virus during long-term follow-up. Appearance of HGV-E2 antibody was associated with the clearance of HGV viraemia. An abnormal ALT level was noted to depend on HCV infection but not on HGV infection in both the acute and chronic phases of transfusion-associated hepatitis.
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MESH Headings
- Acute Disease
- Adult
- Antigens, Viral/immunology
- Female
- Flaviviridae/genetics
- Flaviviridae/immunology
- Follow-Up Studies
- Hepacivirus
- Hepatitis Antibodies/blood
- Hepatitis Antibodies/immunology
- Hepatitis C/physiopathology
- Hepatitis C Antibodies/blood
- Hepatitis, Viral, Human/blood
- Hepatitis, Viral, Human/epidemiology
- Hepatitis, Viral, Human/immunology
- Hepatitis, Viral, Human/physiopathology
- Humans
- Male
- Middle Aged
- Prevalence
- RNA, Viral/blood
- Transfusion Reaction
- Viral Envelope Proteins/immunology
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Affiliation(s)
- E Tanaka
- Second Department of Internal Medicine, Shinshu University School of Medicine, Matsumoto, Japan
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45
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Zhelezova GZ, Karaivanova LA. GB virus C/hepatitis G virus--- is it a novel human 'hepatitis' virus? Clin Microbiol Infect 1998; 4:677-681. [PMID: 11864274 DOI: 10.1111/j.1469-0691.1998.tb00651.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Nishizawa T, Okamoto H, Konishi K, Yoshizawa H, Miyakawa Y, Mayumi M. A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology. Biochem Biophys Res Commun 1997; 241:92-7. [PMID: 9405239 DOI: 10.1006/bbrc.1997.7765] [Citation(s) in RCA: 839] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
By means of representational difference analysis, a viral clone (N22) of 500 nucleotides was isolated from serum of a patient (TT) with posttransfusion hepatitis of unknown etiology. The N22 clone showed a poor homology to any reported sequences. Oligonucleotide primers were deduced from the N22 sequence for detecting it by polymerase chain reaction. N22 sequence in serum banded at a sucrose density of 1.26 g/cm3, indicating its association with a viral particle which was designated TT virus (TTV). Since nucleic acids of TTV were sensitive to DNase I, it would be a DNA virus. TTV DNA was detected in sera from three of the five patients with posttransfusion non-A to G hepatitis, including the index case (TT). TTV DNA titers closely correlated with aminotransferase levels in the three patients. These results indicate that TTV would be a novel DNA virus with a possible capacity to induce posttransfusion non-A to G hepatitis.
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Affiliation(s)
- T Nishizawa
- Immunology Division, Jichi Medical School, Tochigi-Ken, 329-04, Japan
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47
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Raengsakulrach B, Ong-aj-yooth L, Thaiprasert T, Nilwarangkur S, Ong-aj-yooth S, Narupiti S, Thirawuth V, Klungthong C, Snitbhan R, Vaughn DW. High prevalence of hepatitis G viremia among kidney transplant patients in Thailand. J Med Virol 1997; 53:162-6. [PMID: 9334928 DOI: 10.1002/(sici)1096-9071(199710)53:2<162::aid-jmv9>3.0.co;2-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Patients receiving kidney transplants (KT) are at high risk for blood borne viral infections. To determine the prevalence of a recently discovered hepatitis G virus (HGV) in this patient group, reverse transcription-polymerase chain reaction (RT-PCR) employing primers derived from the NS5 region of the viral genome was utilized. HGV RNA was detected in 40 of 94 KT patients (43%), as compared to 3 of 69 healthy subjects (4.3%). Cocirculation of HGV and hepatitis C virus (HCV) RNA was detected in 12 patients (13%). Comparison of patients with and without HGV revealed that the former had received hemodialysis before transplantation for a significantly longer duration than the latter (28 vs. 17 months, respectively; P < 0.05). The amount of blood transfused and mean levels of liver enzymes, including alkaline phosphatase, alanine transaminase, and aspartate transaminase, were the same in both groups. Sequence analysis of 275-base pair DNA clones obtained from 2 patients revealed approximately 92% sequence homology to the published HGV and GB virus C sequences. These results suggested that HGV infection among Thai KT patients was high and the role of HGV in causing liver disease remains to be determined.
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Affiliation(s)
- B Raengsakulrach
- Department of Virology, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.
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48
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Moaven LD, Locarnini SA, Bowden DS, Kim JP, Breschkin A, McCaw R, Yun A, Wages J, Jones B, Angus P. Hepatitis G virus and fulminant hepatic failure: evidence for transfusion-related infection. J Hepatol 1997; 27:613-9. [PMID: 9365036 DOI: 10.1016/s0168-8278(97)80077-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND/AIMS In the majority of cases of fulminant "viral" hepatitis in Australia, no known aetiological agent can be isolated. We have examined the possible role of the recently discovered hepatitis G virus (HGV) in such cases. METHODS An HGV specific reverse transcription polymerase chain reaction (RT-PCR) was performed on pre- and post-liver transplant serum from 14 patients who were referred for transplantation at our unit between 1989 and 1995 for unexplained fulminant hepatic failure. Eleven patients successfully underwent transplantation and three died while waiting for a suitable donor organ. Hepatitis viruses A-E were excluded by standard serological and PCR based testing. HGV RT-PCR was also performed on 21 other, randomly selected, liver transplant recipients ("controls"). RESULTS The 14 fulminant cases were HGV RT-PCR negative prior to transplantation while five of 21 controls were positive. Post-transplant, eight of the 11 fulminant patients were found to be HGV RT-PCR positive and the same five controls remained HGV RT-PCR positive. In three of the eight fulminant patients the HGV infection resolved. CONCLUSIONS Our data indicate that HGV infection is unlikely to be responsible for fulminant hepatitis and that it is probably acquired from blood and/or blood products during the transplantation process. Furthermore, long-term carriage of HGV post-transplant is not associated with clinically apparent liver disease.
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Affiliation(s)
- L D Moaven
- Victorian Infectious Diseases Reference Laboratory, Fairfield Hospital, Melbourne, Australia
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Huang SN, Chen TC, Tsai SL, Liaw YF. Histopathology and pathobiology of hepatotropic virus-induced liver injury. J Gastroenterol Hepatol 1997; 12:S195-217. [PMID: 9407339 DOI: 10.1111/j.1440-1746.1997.tb00502.x] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The present report concerns current knowledge regarding immunopathogenesis that can be applied in the interpretation of histopathological changes in acute and chronic viral hepatitis. The histopathological features of viral hepatitis have not been changed and light microscopic examination remains essential for making a diagnosis and classification of chronic hepatitis and for the provision of objective parameters on grading and staging. However, new understanding and knowledge of viral pathogenesis, host immune responses, the biological behaviour of the causative viral agents and, in particular, viral interference in multiple hepatotropic viral infections must be taken into consideration in the interpretation of histopathological and immunopathological findings of liver tissues. This report also presents some histopathological analyses on multiple hepatotropic viral infections. It can be concluded that the diagnostic histological criteria for acute hepatitis remain applicable in such settings. However, the cause of acute flare up in chronic hepatitis could not be determined without clinical, virological and serological information. Routine histopathology cannot distinguish a new infection from an acute exacerbation due to a high level of viral replication or mutant virus. A repertoire of immunocytochemical stainings for viral antigens is helpful, but caution must be exercised in suggesting a specific viral aetiology due to the fact that suppression of pre-existing viral antigens can be pronounced when the new or concurrent infection is hepatitis C virus related.
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Affiliation(s)
- S N Huang
- Department of Pathology, Sunnybrook Health Science Centre, University of Toronto, North York, Ontario, Canada
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Dussol B, Charrel R, De Lamballerie X, Berthezene P, Brunet P, De Micco P, Raoult D, Berland Y. Prevalence of hepatitis G virus infection in kidney transplant recipients. Transplantation 1997; 64:537-9. [PMID: 9275127 DOI: 10.1097/00007890-199708150-00029] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND We investigated the prevalence, risk factors, and consequences of hepatitis G virus (HGV) infection in 87 kidney transplant recipients. METHODS Infection was diagnosed with reverse transcriptase polymerase chain reaction using primers in the NS3 region of the viral genoma. RESULTS Twenty-four patients (27.5%) were HGV RNA positive (HGV+ group) and 63 patients (72.5%) were HGV RNA negative (HGV- group). No statistically significant differences were found between the two groups for age, sex, transplantation and hemodialysis duration, number of kidney transplantations, serum creatinine, history of transfusions, hepatitis B and C virus infections, and percentage of patients having suffered from acute rejection. Acute and chronic hepatitis were not more prevalent in the HGV+ group than in the HGV- group. CONCLUSIONS HGV infection is highly prevalent in kidney transplant recipients but does not alter liver or kidney functions. HGV contamination may be linked to nosocomial transmission during long-term hemodialysis.
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Affiliation(s)
- B Dussol
- Service de Néphrologie et Hémodialyse, Hôpital Sainte Marguerite, Marseille, France
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